Influence of 13-cis and all-trans retinoic acid on rat embryonic development in vitro: correlation with isomerisation and drug transfer to the embryo.

In vitro experiments using whole rat embryo cultures show that all-trans retinoic acid (all-trans RA) administered at low concentrations (30 ng/ml culture medium) is 10 times more active than 13-cis retinoic acid (13-cis RA) and 3 times more active when administered at high concentrations (1000 ng/ml culture medium). Morphological investigation of the embryos shows that both substances directly influence embryonic development in an identical manner. Isomerisation products of the administered compounds (all-trans RA from 13-cis RA and vice versa) were detected by HPLC both in the culture medium and the embryo. Correlation of embryonic retinoid concentration with the observed effects led us to suggest that the isomerisation to all-trans RA is crucial in regard to 13-cis RA-induced abnormal embryonic development. A 100% effect can be induced in vitro with very low amounts of all-trans RA (7.2 ng/g) in the embryo.